RESEARCH QUESTION

The objective of this investigation is to assess the benefit of bisphosphonates, teriparatide, and denosumab in comparison with each other in the treatment of women with postmenopausal osteoporosis with regard to patient-relevant outcomes. The research question includes an assessment of bisphosphonates in comparison with each other.

CONCLUSION

Given the available evidence, the following individual comparisons were taken into account in the benefit as-sessment: denosumab versus bisphosphonates, teriparatide versus risedronate as well as bisphosphonates in com-parison with each other. For risedronate, the data transmission by the manufacturer was incomplete. Publication bias likely arose with respect to the risedronate intervention. Consequently, no proof, indication, or hint of benefit or harm is derived for the intervention of risedronate (except for a hint of lesser benefit from the comparison of teriparatide versus risedronate). In the comparison of teriparatide versus risedronate, the incompleteness of the manufacturer docu-ments was irrelevant because all studies were available on this comparison. The available evidence for patient-relevant outcomes is deemed limited overall. The available evidence was insufficient, particularly for the outcomes of pain, functional limitations, health-related quality of life, osteonecrosis of the jaw, and symptomatic atypical femoral fractures. COMPARISON OF DENOSUMAB VERSUS BISPHOSPHONATES: For the comparison of denosumab versus bisphosphonates, the available data allow drawing robust conclu-sions only in comparison with the drug zoledronate. The evidence shows the following: No hint of greater benefit or harm resulted from the available data for the outcomes of all-cause mortality, fractures in the hip area, distal radius fractures, symptomatic vertebral fractures, nonvertebral symptomatic fractures, serious adverse events (SAEs), discontinuation due to adverse events (AEs) as well as AEs and SAEs of the gastrointestinal tract. For the outcomes of pain, functional limitations, health-related quality of life, osteonecrosis of the jaw, and symptomatic atypical femoral fractures, no data usable for the comparison of denosumab versus bisphosphonates were available; therefore, no hint of greater benefit or harm resulted for any of them. In the overall weighing of benefit and harm, there was no hint of greater or lesser benefit or harm for treatment with denosumab in comparison with zoledronate across outcomes. COMPARISON OF TERIPARATIDE VERSUS RISEDRONATE: For the comparison of teriparatide versus risedronate, which can be conducted given the available data, the evidence shows the following: For the outcome of symptomatic vertebral fractures, there was a hint of greater benefit of teriparatide ver-sus risedronate. For the outcome of AEs of the gastrointestinal tract, there was a hint of greater harm from teriparatide ver-sus risedronate. No hint of greater benefit or harm was found on the basis of the available data for the outcomes of all-cause mortality, fractures in the hip area, distal radius fractures, nonvertebral symptomatic fractures, pain, SAEs, discontinuation due to AEs, osteonecrosis of the jaw, and symptomatic atypical femoral fractures as well as SAEs of the gastrointestinal tract. No data were available for the outcomes of functional limitations or health-related quality of life; this re-sulted in no hint of greater harm or benefit. Overall, the favourable effect for teriparatide in comparison with risedronate in the outcome of symptomatic vertebral fractures is therefore contrasted by an unfavourable effect for teriparatide in comparison with risedronate in the outcome of AEs of the gastrointestinal tract. Given the fact that the outcome of symptomatic vertebral frac-tures showed a substantial effect in favour of teriparatide (upper limit of the 95% confidence interval: 0.58), while the disadvantage was marginal in the outcome of AEs of the gastrointestinal tract (95% confidence interval: [1.01; 1.57]) and not present in SAEs of the gastrointestinal tract, the overall weighing of benefit and harm across out-comes resulted in a hint of greater benefit of teriparatide versus risedronate. BISPHOSPHONATES IN COMPARISON WITH EACH OTHER: For the comparison of bisphosphonates with each other, robust conclusions based on the available data can be drawn only for the drugs of alendronate and ibandronate. The evidence shows the following: No hint of greater benefit or harm was found based on the available data for the outcomes of fractures in the hip area, distal radius fractures, nonvertebral symptomatic fractures, SAEs, discontinuation due to AEs, or AEs and SAEs of the gastrointestinal tract. No data were available for the outcomes of all-cause mortality, symptomatic vertebral fractures, pain, func-tional limitations, health-related quality of life, osteonecrosis of the jaw, and symptomatic atypical femoral frac-tures; this resulted in no hint of greater benefit or harm for any of them. In the overall weighing of benefit and harm, there was no hint of greater or lesser benefit or harm of alendro-nate versus ibandronate across outcomes.